The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Cancer Sci. 2023 Jul;114(7):2739-2749. doi: 10.1111/cas.15801. Epub 2023 Apr 12.
Tumor angiogenesis plays an important role in the development of cancer as it allows the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination to distant organs. Although anti-angiogenic therapy (AAT) has been approved for treating various advanced cancers, this potential strategy has limited efficacy due to resistance over time. Therefore, there is a critical need to understand how resistance develops. Extracellular vesicles (EVs) are nano-sized membrane-bound phospholipid vesicles produced by cells. A growing body of evidence suggests that tumor cell-derived EVs (T-EVs) directly transfer their cargoes to endothelial cells (ECs) to promote tumor angiogenesis. Importantly, recent studies have reported that T-EVs may play a major role in the development of resistance to AAT. Moreover, studies have demonstrated the role of EVs from non-tumor cells in angiogenesis, although the mechanisms involved are still not completely understood. In this review, we provide a comprehensive description of the role of EVs derived from various cells, including tumor cells and non-tumor cells, in tumor angiogenesis. Moreover, from the perspective of EVs, this review summarized the role of EVs in the resistance to AAT and the mechanisms involved. Due to their role in the resistance of AAT, we here proposed potential strategies to further improve the efficacy of AAT by inhibiting T-EVs.
肿瘤血管生成在癌症的发展中起着重要作用，因为它允许氧气、营养物质和生长因子的输送以及肿瘤向远处器官的扩散。尽管抗血管生成治疗（AAT）已被批准用于治疗各种晚期癌症，但由于随着时间的推移产生了耐药性，这种潜在的策略效果有限。因此，迫切需要了解耐药性是如何发展的。细胞外囊泡（EVs）是由细胞产生的纳米大小的膜结合磷脂囊泡。越来越多的证据表明，肿瘤细胞来源的 EVs（T-EVs）直接将其 cargo 转移到内皮细胞（ECs）以促进肿瘤血管生成。重要的是，最近的研究报告称，T-EVs 可能在 AAT 耐药性的发展中起主要作用。此外，研究表明，非肿瘤细胞来源的 EVs 在血管生成中起作用，尽管涉及的机制仍不完全清楚。在这篇综述中，我们全面描述了来自各种细胞（包括肿瘤细胞和非肿瘤细胞）的 EVs 在肿瘤血管生成中的作用。此外，从 EVs 的角度来看，本文综述了 EVs 在 AAT 耐药性中的作用及其涉及的机制。由于它们在 AAT 耐药性中的作用，我们在这里提出了通过抑制 T-EVs 进一步提高 AAT 疗效的潜在策略。
